PROJECT SUMMARY Low back pain (LBP) is a common and costly condition. Spinal manipulative therapy (SMT) is a common mind body intervention for individuals with LBP. Although SMT for LBP has been examined in numerous clinical studies, the literature on SMT remains unclear and even contradictory as to the effectiveness of this treatment. Studies that have supported SMT have generally found relatively small treatment effects. Many reasons have been offered for the inconsistent research literature and small effect sizes of SMT. A primary rationale offered is that the SMT protocols used in clinical research are not optimal, primarily due to a lack of understanding of the underlying mechanisms explaining the clinical benefits of SMT realized by some patients with LBP. The prior work of this research team has identified two mechanisms explaining the therapeutic effects of SMT. These effects are a reduction in spinal stiffness and improved activation of the lumbar multifidus muscle. Our research team has also developed accurate, non-invasive methods to measure these effects and their response to SMT. Our model identifying these two mechanisms has been validated in a second patient sample. Our overall goal in this proposal is to optimize SMT treatment protocols for patients with LBP. Our optimization strategy will evaluate SMT combined with other treatments known to modulate the same signals that underlie the clinical effects of SMT assessing both mechanistic (stiffness, lumbar multifidus activation) and patient-centered (function and pain) outcomes. In this project we will use innovative methodology to efficiently evaluate the effects of various individual treatment components towards an overall effect; identifying which components are contributing to the target outcomes and which, if any, may be discarded. We will provide 2 sessions of SMT to all participants. We will then randomize subjects stratified by responder status to a treatment group for an additional 3 weeks using a factorial design to evaluate different combinations of intervention components (muscle activation exercise, spinal mobilizing exercise, additional SMT) that work on the same pathways that modulate the same effects (spinal stiffness and muscle activation). Outcomes will include spinal stiffness and muscle activation measures as well as patient-reported outcomes assessed at baseline, and after 1 week, 4 weeks and 3 months. Results of this project will provide optimized SMT protocols that will be ready for application in future randomized controlled trials examining the efficacy and effectiveness of SMT.